Keeping weight off after stopping GLP-1s using metformin with or without rapamycin or low‑dose naltrexone

Effectiveness of Alternative Therapies in Maintaining Weight Loss Achieved by GLP-1 Medications Post-Cessation: A Randomized, Controlled Trial

Phase2; Phase3 Interventional AgelessRx · NCT07092618

This trial will test whether metformin alone or combined with low‑dose rapamycin or low‑dose naltrexone helps adults 40–85 maintain weight loss after they stop GLP‑1 medications.

Quick facts

PhasePhase2; Phase3
Study typeInterventional
Enrollment150 (estimated)
Ages40 Years to 85 Years
SexAll
SponsorAgelessRx Industry-sponsored
Locations1 site (Chicago, Illinois)
Trial IDNCT07092618 on ClinicalTrials.gov

What this trial studies

This is a randomized, controlled Phase 2/3 trial at a single AgelessRx site comparing four arms: control (no alternative medication), metformin, metformin plus rapamycin, and metformin plus low‑dose naltrexone. Eligible AgelessRx patients aged 40–85 with BMI ≥22 who have used GLP‑1s for at least three months and lost ≥15 lb will be randomized and followed during a six‑month period after gradual GLP‑1 cessation. The main outcome is percent weight regain over six months, with secondary outcomes including metabolic markers such as HbA1c and other safety measures. The trial uses repurposed, commonly available medications to test practical strategies for weight maintenance after stopping GLP‑1 therapy.

Who should consider this trial

Good fit: Ideal candidates are AgelessRx patients aged 40–85 with BMI ≥22 who have been on GLP‑1 therapy for at least three months and lost at least 15 pounds and who plan to discontinue GLP‑1s.

Not a fit: Patients with prior bariatric surgery, contraindications to metformin/rapamycin/naltrexone, recent use of other weight‑loss drugs, significant psychiatric illness, or who are pregnant/breastfeeding are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, the regimen could offer a low‑cost, clinic‑based way to reduce weight regain and improve metabolic measures for people stopping GLP‑1 drugs.

How similar studies have performed: Metformin has some prior evidence for modest metabolic and weight effects, but using metformin combined with rapamycin or low‑dose naltrexone specifically to prevent weight regain after GLP‑1 cessation is largely novel and not established in randomized trials.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

* Existing AgelessRx patient
* Adults (40 - 85 years of age)
* Any sex
* Any ethnicity
* BMI ≥ 22 kg/m\^2
* Have been on GLP-1s (Wegovy, Ozempic, or a compounded form of GLP-1s) for at least three months before study initiation
* Have lost at least 15 lbs during their GLP-1 use

Exclusion Criteria:

* Individuals who are denied a longevity product by the AgelessRx medical team will not be asked to participate in any product specific test(s) or questionnaire(s)
* History of bariatric surgery
* Use of weight-loss medications other than GLP-1s within the past 6 months
* Age \<40 years
* Contraindications to naltrexone, metformin, or rapamycin
* Significant psychiatric illness that may affect participation
* Pregnant or breastfeeding individuals

Where this trial is running

Chicago, Illinois

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions LongevityGLP-1GeroscienceAgingHealthy Aging
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.